新疆和田地区维吾尔族妇女宫颈癌组织中HPVDNA的测定

目的：研究我国宫颈癌高发区新疆和田地区维族妇女宫颈癌发病与人类乳头瘤病毒（HPV）的关系。方法：对50例新疆和田地区维族宫颈癌患组织标本采用PCR（聚合酶联反应）技术,检测HPV－C（总的HPC）,HPV16,HPV18及HPV6／11。结果：HPV－C,HPV16,HPV18及HPV6／11在宫颈癌病人中的检出率分别为80．0％,66．0％,10．0％,0％,HPV16在HPV阳性患者中占的比例为91．4％,鳞癌HPV16阳性率明显地腺癌,而腺癌HPV18检出率明显高于鳞癌（P＜0．05）。HPV在感染率及HPV16阳性率与宫颈癌临床分期及病理分级之间无显著差异。结论：HPV感染与我国宫颈癌高发区新疆维族妇女宫颈癌发有密切关系,其中,HPV16感染在新疆和田地区维族妇女宫颈癌发病中起主要作用,HPV感染与宫颈癌临床全期及病理分级无关。     

Comparison of risk factors for invasive squamous cell carcinoma and adenocarcinoma of the cervix: collaborative reanalysis of individual data on 8,097 women with squamous cell carcinoma and 1,374 women with adenocarcinoma from 12 epidemiological studies

Squamous cell carcinomas account for about 80% of cancers of the uterine cervix, and the majority of the remainder are adenocarcinomas. There is limited evidence on the extent to which these histological types share a common etiology. The International Collaboration of Epidemiological Studies of Cervical Cancer has brought together and combined individual data on 8,097 women with invasive squamous cell carcinoma, 1,374 women with invasive adenocarcinoma and 26,445 women without cervical cancer (controls) from 12 epidemiological studies. Compared to controls, the relative risk of each histological type of invasive cervical cancer was increased with increasing number of sexual partners, younger age at first intercourse, increasing parity, younger age at first full-term pregnancy and increasing duration of oral contraceptive use. Current smoking was associated with a significantly increased risk of squamous cell carcinoma (RR = 1.50, 95% CI: 1.35-1.66) but not of adenocarcinoma (RR = 0.86 (0.70-1.05)), and the difference between the two histological types was statistically significant (case-case comparison p < 0.001). A history of screening (assessed as having had at least one previous nondiagnostic cervical smear) was associated with a reduced risk of both histological types, but the reduction was significantly greater for squamous cell carcinoma than for adenocarcinoma (RR = 0.46 (0.42-0.50) and 0.68 (0.56-0.82), respectively; case-case comparison, p = 0.002). A positive test for cervical high-risk HPV-DNA was a strong risk factor for each histological type, with 74% of squamous cell carcinomas and 78% of adenocarcinomas testing positive for HPV types 16 or 18. Squamous cell and adenocarcinoma of the cervix share most risk factors, with the exception of smoking.     

Smoking and cervical cancer: pooled analysis of the IARC multi-centric case–control study

BACKGROUND: Smoking has long been suspected to be a risk factor for cervical cancer. However, not all previous studies have properly controlled for the effect of human papillomavirus (HPV) infection, which has now been established as a virtually necessary cause of cervical cancer. To evaluate the role of smoking as a cofactor of progression from HPV infection to cancer, we performed a pooled analysis of 10 previously published case-control studies. This analysis is part of a series of analyses of cofactors of HPV in the aetiology of cervical cancer. METHODS: Data were pooled from eight case-control studies of invasive cervical carcinoma (ICC) and two of carcinoma in situ (CIS) from four continents. All studies used a similar protocol and questionnaires and included a PCR-based evaluation of HPV DNA in cytological smears or biopsy specimens. Only subjects positive for HPV DNA were included in the analysis. A total of 1463 squamous cell ICC cases were analyzed, along with 211 CIS cases, 124 adeno- or adeno-squamous ICC cases and 254 control women. Pooled odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression models controlling for sexual and non-sexual confounding factors. RESULTS: There was an excess risk for ever smoking among HPV positive women (OR 2.17 95%CI 1.46-3.22). When results were analyzed by histological type, an excess risk was observed among cases of squamous cell carcinoma for current smokers (OR 2.30, 95%CI 1.31-4.04) and ex-smokers (OR 1.80, 95%CI 0.95-3.44). No clear pattern of association with risk was detected for adenocarcinomas, although the number of cases with this histologic type was limited. CONCLUSIONS: Smoking increases the risk of cervical cancer among HPV positive women. The results of our study are consistent with the few previously conducted studies of smoking and cervical cancer that have adequately controlled for HPV infection. Recent increasing trends of smoking among young women could have a serious impact on cervical cancer incidence in the coming years.     

Diagnostic, endocrinological, behavioral, and DNA ploidy differences between squamous cell and adenomatous carcinoma of the cervix uteri

The objective of this study was to compare behavioral and hormonal risk factors, and cancer characteristics in squamous cell and adenocarcinoma of the cervix uteri. The study included 45 women with adenocarcinoma and 190 consecutive women with squamous cell carcinoma of the cervix uteri diagnosed between 1984 and 1990. In addition to routine diagnostic procedures, DNA from biopsies was analyzed with flow cytometry to identify the S-phase fraction as a measure of cancer growth. Serum progesterone and estradiol were measured, and ever hormonal use and smoking were recorded. Ten-year mortality was estimated. There was no significant difference in age at diagnosis. Women with adenocarcinoma, compared with those with squamous epithelial carcinoma, had a significantly shorter duration of ever contraceptive use, were less likely to smoke (nonsignificant), had a lower cancer stage, were less likely to have an S-phase fraction of more than 16%. and had a higher progesterone value (if premenopausal). The results suggest that there are some different risk factors in adenocarcinoma and squamous cell carcinoma of the cervix uteri.     

HPV 16 in multiple neoplastic lesions in women with CIN III

Paraffin embedded material of multiple primary cancers and other hyperplastic tumours from fifteen patients were analyzed by PCR and in situ hybridization for the presence of HPV DNA in the lesions. All patients had also high grade cervical intraepithelial dysplasia (CIN III) and breast carcinomas and were selected from a previous study enrolling 46 women with CIN III and breast carcinomas. HPV 16 was detected by PCR in 8/15 patients (53%), with eleven HPV 16 positive tumours. HPV 16 was detected in two malignant melanomas, one basal cell carcinoma, one squamous cell carcinoma of the vulva, one Bowen disease of the vulva, two high grade vaginal intraepithelial neoplasias, one cancer corporis uteri, one bronchial carcinoma and two lymphomas. Three cases, two high grade vaginal intraepithelial neoplasia and a squamous cell carcinoma of the vulva, were also reported to be positive by in situ hybridization. 5/8 patients (63%) with HPV 16 positive second cancers had also HPV 16 positive breast carcinomas. All fifteen patients with second cancers after CIN III had HPV 16 positive CIN III lesions; 53% of the patients had also a familial cancer history. We assume that HPV 16 may be involved in the development of different second cancers in women with HPV 16 positive CIN III.     

Papillomaviruses causing cancer: evasion from host-cell control in early events in carcinogenesis

During the past 20 years, several types of human papillomaviruses (HPVs) have been identified that cause specific types of cancers. The etiology of cancer of the cervix has been linked to several types of HPV, with a high preponderance of HPV16. The role of these virus infections has been established 1) by the regular presence of HPV DNA in the respective tumor biopsy specimens, 2) by the demonstration of viral oncogene expression (E6 and E7) in tumor material, 3) by the identification of transforming properties of these genes, 4) by the requirement for E6 and E7 expression for maintaining the malignant phenotype of cervical carcinoma cell lines, 5) by the interaction of viral oncoproteins with growth-regulating host-cell proteins, and 6) by epidemiologic studies pointing to these HPV infections as the major risk factor for cervical cancer development. In addition to cancer of the cervix, a major proportion of anal, perianal, vulvar, and penile cancers appears to be linked to the same HPV infections. In addition, close to 20% of oropharyngeal cancers contain DNA from the same types of HPV. Recent evidence also points to a possible role of other HPV infections in squamous cell carcinomas of the skin. This review covers recent developments in understanding molecular mechanisms of HPV carcinogenesis, mainly discussing functions of viral oncoproteins and the regulation of viral oncogenes by host-cell factors. Modifications in host-cell genes, most likely engaged in the control of HPV gene expression in proliferating cells, emerge as important events in HPV-mediated carcinogenesis.     

宫颈癌高发区新疆维吾尔族妇女宫颈癌组织中HPV DNA的测定

目的 研究我国宫颈癌高发区新疆维吾尔自治区维族妇女宫颈癌发病与人类乳头状瘤病毒（HPV）的关系。方法 对75例新疆维吾尔族宫颈癌患者癌组织及20例正常宫颈组织,采用PCR（聚合酶链反应）技术检测HPV－C（总的HPV）、HPV16、HPV18及HPV6／11。结果 HPV－C、HPV16、HPV18及HPV6／11在宫颈癌患者及正常宫颈组织中的检出率分别为86．7％、72．0％、12．0％、0及20．0％、10．0％、0、10．0％。HPV16在HPV阳性患者中所占的比例为83．1％,宫颈癌患者中HPV－C、HPV16检出率明显高于正常对照组,鳞癌HPV16阳性率明显高于腺癌,而腺癌HPV18检出率明显高于鳞癌（P＜0．05）。HPV总感染率及HPV16阳性率,在不同临床分期及不同病理分级宫颈癌组织间无显著性差异。结论 HPV感染与我国宫颈癌高发区新疆维吾尔族妇女宫颈癌发病有密切相关,其中HPV16感染在其发病中起主要作用,但HPV感染对宫颈癌的进展影响不大。     

Mortality of wives of men dying with cancer of the penis.

711 women were identified who in 1939 were married to men who died with cancer of the penis in England and Wales during the period 1964 to 1973. The records of women were traced through the National Health Service Central Register and, by January 1975, 378 (53%) were found to have died. Expected numbers of deaths from all causes, all cancers and from some specific cancers were calculated assuming the women to have the same mortality rates as the general population of England and Wales. The total number of deaths (378) was close to the number expected (366-8) but there was a slight excess of deaths from cancer (89 against 76.5 expected). Of the individual sites examined only cancer of the cervix showed a statistically significant excess (11 deaths against 3.9 expected, P = 0.002). This finding is similar to those reported in two other studies of the wives of men with cancer of the penis. On the basis of these studies it is suggested that some cases of cancer of the cervix and cancer of the penis may have a common aetiology. Other epidemiological characteristics of the two diseases do not show a marked similarity.     

Estrogen and progesterone receptor expression in HPV-positive and HPV-negative cervical carcinomas

Human papillomavirus (HPV) is widely accepted as the main cause of cervical cancer. However, the presence of HPV DNA does not inescapably lead to the development of the cancerous phenotype of the infected cell. Therefore, it is considered that the induction of full cancerous expression of HPV requires additional cofactors. The aim of this study was to assess the expression of estrogen receptor α (ERα) and progesterone receptor (PR) in archived tissue blocks of squamous cell carcinoma and adenocarcinoma of the uterine cervix and to ascertain whether expression of these receptors is associated with the presence of HPV DNA. The investigation was performed using formalin-fixed, paraffin-embedded cervical cancer specimens obtained from 250 women who underwent surgery for histologically confirmed neoplastic lesions. The control group consisted of normal cervical tissues obtained from 50 patients who underwent myomectomy. The results of this study revealed that the expression of ER and PR in planoepithelial cancers and adenocarcinomas of the cervix were decreased to undetectable levels. Only in singular cases in the pattern of staining the expression of ER and PR was noted. In stromal cells of the tested neoplasms, higher expression of both types of receptors was found. Comparison of the expression of ER and PR in the staining pattern and stroma of both squamous cell carcinoma and adenocarcioma of the cervix, showed statistically higher expression in the stromal cells. Strong expression (+1, +2, +3) of ER and PR was noted in the stromal cells irrespective of HPV infection, histopathological type of cancer, and clinical and histopathological grade.     

Human papillomavirus in head and neck cancer: Molecular biology and clinicopathological correlations

Human papillomaviruses are known to cause cancers of the cervix and other anogenital tract sites. Epidemiologic and molecular pathology studies have also suggested that HPV infection may be associated with cancers of the head and neck. Modes of transmission of HPV infection in the head and neck region have not been fully resolved; however, perinatal transmission and an association between sexual behavior and risk for HPV-positive cancers have been presented.Among the HPV types infecting the mucosa, high-risk, intermediate-risk and low-risk genotypes are defined, depending on their presence in carcinoma or precursor lesions. The phylogenic groups of HPVs also showed a definite correlation with the morphology of head and neck tumors. The groups A6, A7, and A9 include viruses that are frequently demonstrated in basaloid and verrucosus squamous cell carcinomas known to associate with HPV infection. Integration of HPV DNA into the host cell genome occurs early in cancer development and is an important event in malignant transformation.There is a trend for patients with HPV-positive tumors to be nondrinkers or light drinkers, the majority of these patients are females, and the median age is lower than in the case of HPV-negative tumors, but this latter difference was not always statistically significant. In the Kaplan-Meier survival model, the HPV-positive verrucous and basaloid squamous cell carcinomas showed better survival rates than the HPV-negative typical squamous cell carcinomas. An increased radiocurability of HPV-positive head and neck squamous cell carcinoma (HNSCC) has also been demonstrated.     

Host genetic control of HPV 16 titer in carcinoma in situ of the cervix uteri

Cervical cancer is strongly associated with infection by oncogenic forms of human papillomavirus (HPV). Although most women are able to clear an HPV infection, some develop persistent infections that may lead to cancer. The determinants of persistent infection are largely unknown. We have previously shown that women developing carcinoma in situ of the cervix uteri have higher titers of HPV 16 long before development of cervical neoplasia, indicating that the immune response to HPV is important in determining the outcome of an infection. The HLA class II alleles DRB1*1501 and DQB1*0602 have previously been associated with an increased risk of HPV infection, and carriers of these alleles also tend to have more long-term infections. Together these results indicate that certain HLA alleles may affect the ability to control the HPV copy number. To evaluate this possibility, we studied the HLA class II DRB1*1501-DQB1*0602 haplotype, as well as the alleles individually, and the HPV 16 titer in 928 women from a retrospective case-control study (441 cases and 487 controls). Carriers of the haplotype DRB1*1501-DQB1*0602 allele have a significantly higher HPV 16 titer compared to noncarriers (t-test with unequal variance, p = 0.017). An association was found between the HLA haplotype carrier frequency and HPV 16 titer (Mantel-Haenszel statistics p = 0.005). To study whether titer is related to the persistency of infection, women were divided into groups with long-term and short-term infection. A strong correlation is seen between long-term infection and high viral load and between short-term infection and low viral load. These results show that host genetic factors, e.g., variation at the HLA class II loci studied, may affect the immune reaction to the virus and thereby indirectly increase the susceptibility to carcinoma in situ of the cervix uteri.     

Comparison of risk factors for squamous cell and adenocarcinomas of the cervix: a meta-analysis

While most cancers of the uterine cervix are squamous cell carcinomas, the relative and absolute incidence of adenocarcinoma of the uterine cervix has risen in recent years. It is not clear to what extent risk factors identified for squamous cell carcinoma of the cervix are shared by cervical adenocarcinomas. We used data from six case-control studies to compare directly risk factors for cervical adenocarcinoma (910 cases) and squamous cell carcinoma (5649 cases) in a published data meta-analysis. The summary odds ratios and tests for differences between these summaries for the two histological types were estimated using empirically weighted least squares. A higher lifetime number of sexual partners, earlier age at first intercourse, higher parity and long duration of oral contraceptive use were risk factors for both histological types. Current smoking was associated with a significantly increased risk of squamous cell carcinoma, with a summary odds ratio of 1.47 (95% confidence interval: 1.15-1.88), but not of adenocarcinoma (summary odds ratio=0.82 (0.60-1.11); test for heterogeneity between squamous cell and adenocarcinoma for current smoking: P=0.001). The results of this meta-analysis of published data suggest that squamous cell and adenocarcinomas of the uterine cervix, while sharing many risk factors, may differ in relation to smoking. Further evidence is needed to confirm this in view of the limited data available.     

Human Papillomavirus Burden in Different Cancers in Iran: a Systematic Assessment

Certain types of human papillomaviruses (HPVs) are undoubtedly involved in genesis of human malignancies. HPV plays an etiological role in cervical cancer, but also in many vaginal, vulvar, anal and penile cancers, as well as head and neck cancers. In addition, a number of non-malignant diseases such as genital warts and recurrent respiratory papillomatosis are attributable to HPV. Moreover, HPV forms have detected in several other cancers including esophageal squamous cell carcinoma, lung, prostate, ovarian, breast, skin, colorectal and urinary tract cancers, but associations with etiology in these cases is controversial. The aim of this systematic assessment was to estimate the prevalence of HPV infection and HPV types in HPV-associated cancers, HPV-related non-malignant diseases and in cancers that may be associated with HPV in Iran. The present investiagtion covered 61 studies on a variety of cancers in Iranian populations. HPV prevalence was 77.5 % and 32.4% in cervical cancer andhead and neck cancers, respectively. HPV was detected in 23.1%, 22.2%, 10.4%, 30.9%, 14% and 25.2% of esophageal squamous cell, lung, prostate, urinary tract cancers, breast and skin cancers, respectively. HPV16 and 18 were the most frequent HPV types in all cancers. The findings of present study imply that current HPV vaccines for cervical cancer may decrease the burden of other cancers if they are really related to HPV.     

Cervical Adenocarcinoma and Squamous Cell CarcinomaIncidence Trends among Tunisian Women

Introduction: Uterine cervix cancer is an important public health problem in Tunisia. In this study, we reporttrends in the incidence of adenocarcinoma and squamous cell carcinoma of the cervix uteri in the central regionof Tunisia during 1993-2006. Design: Data were obtained from the Cancer Registry of the Center of Tunisiawhich registers invasive cancer cases by active methods. Five-year age-specific rates, crude incidence rates (CR),world age-standardized rates (ASR), percent change (PC) and annual percent change (APC) were calculatedusing annual population data. Results: Among all women cancers, cervix uteri cancer accounted for 5.9% andranked the fourth during the study period with an ASR of 6.9 per 100,000. The ASRs decreased notably with anAPC of -6.7% over the whole period. However, incidence rates of adenocarcinomas have increased during thelast years (APC: +14.4%). Conclusion: The introduction of cytological screening programs has led to a markeddecrease of the incidence rates of cervix uteri cancer among Tunisian women. The data underline the fact thatthe population-based cancer registry is an indispensable tool for providing data for planning and evaluation ofprograms for cancer control.     

Cyclin D1 G870A polymorphism and squamous cell carcinoma of the uterine cervix in Korean women

Though many investigators have reported relationships between the CCND1 polymorphism and susceptibility to various carcinomas, to our knowledge, no report has been issued concerning its relationship with uterine cervical cancer. Thus, we undertook this study to investigate the association between CCND1 polymorphisms and susceptibility to cervical cancer in Korean women. This study was carried on 222 patients with squamous cell carcinoma of uterine cervix and on 314 normal controls. CCND1 genotyping was determined by polymerase chain reaction and restriction fragment length polymorphism. The allelic frequencies of the cases (A, 0.53; G, 0.47) were not significantly different from those of the controls (A, 0.49; G, 0.51) (P=0.238). Regression analysis after adjusting for age showed that the CCND1 G870A genotypes are not related to the risk of squamous cell carcinoma of the uterine cervix. Our findings suggest that the CCND1 polymorphism is not associated with an increased risk of squamous cell carcinoma of uterine cervix in Korean women.     

Development of an in vitro carcinogenesis model of human papillomavirus‐induced cervical adenocarcinoma

Cervical adenocarcinoma (ADC) is the second most common pathological subtype of cervical cancer after squamous cell carcinoma. It accounts for approximately 20% of cervical cancers, and the incidence has increased in the past few decades, particularly among young patients. The persistent infection of high‐risk human papillomavirus (HPV) is responsible for most cervical ADC. However, almost all available in vitro models are designed to study the carcinogenesis of cervical squamous cell carcinoma. To gain better insights into molecular background of ADC, we aimed to establish an in vitro carcinogenesis model of ADC. We previously reported the establishment of an in vitro model for cervical squamous cell carcinoma by introducing defined viral and cellular oncogenes, HPV16 E6 and E7, c‐MYC, and activated RAS to human cervical keratinocytes. In this study, the expression of potential lineage‐specifying factors and/or SMAD4 reduction was introduced in addition to the defined four oncogenes to direct carcinogenesis toward ADC. The cell properties associated with the cell lineage were analyzed in monolayer and organoid cultures and the tumors in mouse xenografts. In the cells expressing Forkhead box A2 (FOXA2), apparent changes in cell properties were observed, such as elevated expression of columnar cell markers and decreased expression of squamous cell markers. Strikingly, the histopathology of tumors expressing FOXA2 resembled cervical ADC, proposing that FOXA2 plays a vital role in dictating the histopathology of cervical cancers.     

Carcinoma of the cervix and tobacco smoking: collaborative reanalysis of individual data on 13,541 women with carcinoma of the cervix and 23,017 women without carcinoma of the cervix from 23 epidemiological studies

Tobacco smoking has been classified as a cause of cervical cancer, but the effect of different patterns of smoking on risk is unclear. The International Collaboration of Epidemiological Studies of Cervical Cancer has brought together and combined individual data on 13,541 women with and 23,017 women without cervical carcinoma, from 23 epidemiological studies. Relative risks (RRs) and 95% confidence intervals (CIs) of carcinoma of the cervix in relation to tobacco smoking were calculated with stratification by study, age, sexual partners, age at first intercourse, oral contraceptive use and parity. Current smokers had a significantly increased risk of squamous cell carcinoma of the cervix compared to never smokers (RR = 1.60 (95% CI: 1.48-1.73), p<0.001). There was increased risk for past smokers also, though to a lesser extent (RR = 1.12 (1.01-1.25)), and there was no clear trend with time since stopping smoking (p-trend = 0.6). There was no association between smoking and adenocarcinoma of the cervix (RR = 0.89 (0.74-1.06) and 0.89 (0.72-1.10) for current and past smokers respectively), and the differences between the RRs for smoking and squamous cell and adenocarcinoma were statistically significant (current smoking p<0.001 and past smoking p = 0.01). In current smokers, the RR of squamous cell carcinoma increased with increasing number of cigarettes smoked per day and also with younger age at starting smoking (p<0.001 for each trend), but not with duration of smoking (p-trend = 0.3). Eight of the studies had tested women for cervical HPV-DNA, and in analyses restricted to women who tested positive, there was a significantly increased risk in current compared to never smokers for squamous cell carcinoma (RR = 1.95 (1.43-2.65)), but not for adenocarcinoma (RR = 1.06 (0.14-7.96)). In summary, smokers are at an increased risk of squamous cell but not of adenocarcinoma of the cervix. The risk of squamous cell carcinoma increases in current smokers with the number of cigarettes smoked per day and with younger age at starting smoking.     

Characterization of HPV subtypes not covered by the nine-valent vaccine in patients with CIN 2-3 and cervical squamous cell carcinoma

Background: As the second most common female malignant tumor, cervical cancer is also one of the most preventable and avoidable cancers. The World Health Organization has launched a global plan to accelerate the elimination of cervical cancer. Therefore, in the era of postvaccine, the role of HPV subtypes in cervical precancerous lesions and cervical cancer that are not covered by vaccine should be further discussed. The purpose of this study was to explore the role of HPV subtypes not covered by the nine-valent vaccine in high-grade cervical precancerous lesions and cervical cancer. Materials and methods: A retrospective analysis was performed on the clinical data of 5220 patients with an HPV infection who were diagnosed and treated in the Department of Gynecology of Shanghai General Hospital between October 2016 and February 2020. In addition, the clinical characteristics of the biopsy results of 470 cases of cervical intraepithelial neoplasia (CIN) 2-3 and 205 cases of cervical squamous cell carcinoma were analyzed. Results: Among patients with HPV subtype infection not covered by the nine-valent vaccine, univariate analysis showed that compared with patients with CIN 2-3, age ≥ 50, not using condom and TCT reported as ASC-H were risk factors for cervical squamous cell carcinoma (P < 0.05). The detection rates of HPV subtype not covered by the nine-valent vaccine in CIN 2-3 and cervical squamous cell carcinoma patients were 7.23% and 6.34%, respectively. Conclusion: In patients with CIN 2-3 and cervical squamous cell carcinoma, the infection rates of HPV subtype not covered by the nine-valent vaccine were 7.23% and 6.34%, respectively. With the increasing popularity of the vaccine, the infection rates of the corresponding HPV subtype decreased; however, HPV subtype infection not covered by the nine-valent vaccine should not be ignored.     

Anal and perianal squamous carcinomas and high‐grade intraepithelial lesions exclusively associated with “low‐risk” HPV genotypes 6 and 11

Anal squamous cell carcinomas are predominantly associated with high‐risk human papillomaviruses (HPVs), particularly HPV 16, similar to cervical, vaginal and vulvar cancers. Although the presence of “low‐risk” HPVs, in particular genotypes 6 and 11, have occasionally been reported in various HPV‐related anogenital cancers, the overall distribution of these genotypes in the anal canal and perianal tissue may differ to that in the cervix. In addition, although the majority of anal and perianal cancers are associated with HPV, some are not; hence, confirmation of direct association of the virus within a lesion is important. Using laser capture microdissection, anal and perianal invasive carcinomas and high‐grade squamous intraepithelial lesions (HSILs) in biopsies previously associated with HPV 6 or 11 alone were isolated from tissue sections and HPV genotype tested. Of seven cases tested, four invasive carcinomas were positive for HPV 6 only, one invasive carcinoma was negative for HPV and two HSILs were positive for HPV 11 only. All samples were confirmed as HPV 16/18 negative using two different DNA targets (E6 and L1). From these results, we confirm that HPV 6 and 11 can occasionally be associated with high‐grade lesion and anal cancer.     

Human papillomavirus 16 infection in adenocarcinoma of the cervix

The impact of the success of organised cervical screening programme results in a steady decline of the incidence of squamous cell carcinoma of the cervix but a concomitant increase in the incidence of the less common histological subtypes, particularly adenocarcinoma of the cervix (ACC). Although Human papillomavirus (HPV) infection is believed to be a necessary cause of cervical cancer, its role in the pathogenesis of ACC is not well established. Established associations between oncogenic strains of HPV and ACC are based on molecular studies carried out on entire tumour block sections. In this study, the cervical adenocarcinoma cells of a 10-year cohort of women diagnosed with ACC were dissected using the PixCell II Laser Microdissecting System to detect the HPV 16 genome sequence using the real-time quantitative polymerase chain reaction to confirm the presence of HPV DNA within ACC cells. By coupling these two sophisticated techniques, the HPV DNA copy number cell could be calculated to investigate its role. The prevalence of HPV 16 infection in this cohort was 24%, which is significantly higher than the control group (chi(2), P=0.014). Women with ACC also had significantly higher HPV DNA copy number per cell compared to the control group (P=0.00007). Higher HPV DNA copy number is associated with risk of developing ACC.